Project Summary ? Driving Biomedical Projects The goal of this renewal of the Proteomics Research Resource is to broadly impact biomedical research by providing the capabilities to obtain higher quality proteomics data from much smaller samples, together with producing more comprehensive quantitative measurements, improving coverage of low abundance components, such as problematic peptide isomers and post translational modifications, and enabling large increases in measurement throughput. These advances will be made in tandem with efforts to assure broad and sustained access to the new capabilities so they will continue to have high impact on biomedical research. To assist in achieving these goals, we have identified nine initial Driving Biomedical Projects (DBPs). These have been selected to both focus the three Technology Research and Development (TR&D) projects on developing solutions to real-world problems and to serve as examples to the wider community on how to use the new technologies in their own research projects. Each DBP will serve as a test-bed for the initial application of new technologies and the earliest stages of community engagement. The nine DBPs represent geographically dispersed collaborators, working on a wide range of biomedically-relevant research topics, and whose work can be greatly enhanced by the application of the new technologies. The DBPs will significantly benefit from all three of the Resource TR&Ds including the capabilities to: manipulate and process much smaller samples (TR&D 1), provide broad and quantitative proteomics data from such samples at higher throughput (TR&D 2), and enable bioinformatics analysis of the resulting data as well as the generation of biological insights (TR&D 3). Working in concert with the TR&D efforts, the DBPs will also provide key impetus for the prioritization of the TR&D activities, will stimulate problem solving, and provide the challenges needed for driving technology developments. They will also drive the integration of the capabilities developed within each of the three Resource TR&Ds. In the course of this renewal, our advances will progressively enable increasingly challenging DBPs. For example, the ability to obtain quantitative high throughput proteomics measurements at the single cell level, would expand the utility of proteomics for entirely new areas of research. Such dramatic advances in capabilities will be initially applied within several current as well as new DBPs. These projects and their success will support our efforts to both educate and increase the awareness within the broader community of our new capabilities. In conjunction with other aspects of the Resource community engagement activities, the DBPs will help assure their broadest and most sustained availability to the research community.